Transfer of human myocarditis into severe combined immunodeficiency mice.

Abstract

Severe combined immunodeficiency (SCID) mice possess neither T nor B lymphocytes and are thus suitable recipients for lymphocytes of different species. Because autoimmune mechanisms are suspected in the pathogenesis of myocarditis (MC), we attempted to determine whether peripheral blood lymphocytes (PBLs) from patients with MC could be transferred into SCID mice and whether they had an autoimmunologic effect. Groups of three mice each were injected intraperitoneally with up to 50 million PBLs from five MC patients with autoantibodies against the adenine nucleotide translocator (ANT), a myocardial autoantigen. The PBLs from three healthy blood donors were used as controls. After 60 days, human PBLs could be demonstrated in the peripheral blood of the SCID mice transfused with the PBLs of MC patients, representing up to 9.9% of the peripheral blood mononuclear cells. The transfused SCID mice sera showed human immunoglobulin levels of up to 3 mg/mL, both IgG and IgM. Autoantibodies against ANT were present in the mice receiving PBLs from MC patients but not from the control subjects. In addition, infiltrating human lymphocytes were present in the hearts of the SCID mice transfused with PBLs from MC patients. The presence of an ongoing autoimmune process in the SCID mice transfused with PBLs from MC patients is suggested by increased levels of soluble interleukin-2 receptor in the serum in contrast to SCID mice transfused with PBLs from healthy blood donors. We conclude that the autoimmune reactions seen in human MC can be transferred to SCID mice by the transfer of PBLs from MC patients. These findings stress the significance of autoimmune mechanisms in the pathogenesis of human MC.